91926-09-9Relevant articles and documents
Mechanochemical activation of disulfide-based multifunctional polymers for theranostic drug release
Shi, Zhiyuan,Song, Qingchuan,G?stl, Robert,Herrmann, Andreas
, p. 1668 - 1674 (2021/02/22)
Drug delivery systems responsive to physicochemical stimuli allow spatiotemporal control over drug activity to overcome limitations of systemic drug administration. Alongside, the non-invasive real-time tracking of drug release and uptake remains challenging as pharmacophore and reporter function are rarely unified within one molecule. Here, we present an ultrasound-responsive release system based on the mechanochemically induced 5-exo-trigcyclization upon scission of disulfides bearing cargo molecules attachedviaβ-carbonate linker within the center of a water soluble polymer. In this bifunctional theranostic approach, we release one reporter molecule per drug molecule to quantitatively track drug release and distribution within the cell in real-time. We useN-butyl-4-hydroxy-1,8-naphthalimide and umbelliferone as fluorescent reporter molecules to accompany the release of camptothecin and gemcitabine as clinically employed anticancer agents. The generality of this approach paves the way for the theranostic release of a variety of probes and drugs by ultrasound.
Hydrogean Peroxide Inducible Acid-Activatable Prodrug for Targeted Cancer Treatment
Liu, Jun,Wang, Jinhua,Si, Shuang,Xu, Jinyi,Xue, Peng
, p. 3231 - 3235 (2021/08/18)
Because some of the potentially most useful boronic acids are inherently unstable in blood plasma and exhibit poor selective retention in tumours, 2-heterocyclic N-methyliminodiacetic acid (MIDA) boronates provide a stable, spacious and highly effective harbor for prodrug conjugates. Herein we report MIDA boronates in conjunction with naphthalene-based fluorophores as suitable compounds for tumour diagnosis by virtue of their remarkable specificity and uniform benchtop stability. The shielding group was found to be effective at imparting stability under physiological conditions (pH 7.4), with rapid release of the drug upon exposure to the acidic microenvironment of the tumor. This approach significantly enhanced the efficiency of drug release and was found to exhibit fewer side effects, thus indicating its great potential for precision therapeutics.
A Concise Total Synthesis of (±)-Camptothecin
Chen, Fen-Er,Huang, Guan-Xin,Liu, Min-Jie,Liu, Qian
, p. E3 (2019/09/07)
A total synthesis of racemic camptothecin, characterized by a concise construction of the ring systems and easy functional group transformation, is described. A domino reaction consisting of a Heck reaction and an aza-intramolecular Michael addition to form the C ring serves as the first key step in the synthesis. The D ring was constructed by a simple Wittig-Horner reaction followed by removal of the protective groups. Hydroxymethylation, demethylation, and lactone formation reactions were performed in one-pot to construct the E ring under hydrobromic acid conditions. This work provides an efficient scheme for further synthetic exploration of camptothecin and its analogues.
Asymmetric total synthesis of (20S)-Camptothecin using a chiral auxiliary strategy
Liu, Qian,Liu, Minjie,Huang, Guangxin,Chen, Fen-er
, p. 2647 - 2651 (2019/04/03)
An asymmetric eight-step total synthesis of (20S)-camptothecin, starting from the known compound tert-butyl (2-chloroquinolin-3-yl)methylcarbamate, is described. A Heck reaction followed by an intramolecular Michael addition to form the C-ring provides the first key step in this synthesis. The construction of the 20(S) chiral center relies on a chiral auxiliary-mediated Michael addition using (2R,5R)-2-tert-butyl-5-ethyl-1,3-dioxolan-4-one as the auxiliary.
Synthesis and antitumor activity of a series of lactone-opened camptothecin derivatives
Zheng, Chao,Li, Ming-Zong,You, Tian-Pa,Tang, Wei-Ping,Lou, Li-Guang
, p. 51 - 61 (2017/10/30)
A series of E-ring lactone-opened camptothecin (CPT) derivatives bearing with terminal aza-heterocyclic groups were synthesized, and their antitumor activity was evaluated both in vitro and in vivo. Hydroxyl-amide analogues with morpholin-4-yl displayed excellent antitumor activity in vitro and efficient inhibition on tumor xenograph model in nude mice. Ester-amide compounds acted less active in vitro cytotoxicity and lower inhibition activity in vivo. Substitutions at 7- and 10- positions favored the antitumor activity.
Host–guest systems based on pH-sensitive acyclic cucurbit[n]urils for controlled release of camptothecin
Lin, Jieling,Yang, Lei,Liao, Xiali,Gao, Chuanzhu,Yang, Bo
, p. 159 - 168 (2019/07/30)
Stimuli-responsive drug delivery systems may provide an effective way to treat cancer as they can release cargoes regularly according to changes in the human microenvironment. In this work, we design and prepare acid-controlled release complexes of camptothecin with three pH-sensitive acyclic cucurbit[n]urils. The inclusion complexes have been characterized by 1H and 2D nuclear magnetic resonance, X-ray powder diffraction, and phase solubility diagram. Cells incubated with complexes have been analyzed by high-content analysis, and cytotoxicity tests have been completed by MTT assay. The results showed that complexes with different binding constants can release the drug substance in the physiological pH environment of cancer cells, maintain good anticancer activity, and have low cytotoxicity. This provides a strategy about targeted and responsive systems of CPT for clinical application.
Visible-Light-Induced Radical Cascade Cyclization: Synthesis of (20S)-Camptothecin, SN-38 and Irinotecan
Yuan, Yao,Dong, Wuheng,Gao, Xiaoshuang,Xie, Xiaomin,Curran, Dennis P.,Zhang, Zhaoguo
, p. 1035 - 1040 (2018/09/25)
(20S)-Camptothecin, irinotecan and SN-38 were successfully synthesized by a photocatalyzed radical cascade cyclization from an N-propargyl iodopyridinone and an arylisonitrile under visible light with a ruthenium catalyst. This synthetic method provided a useful entry into composing camptothecin family of antitumor agents in good yields under mild reaction conditions without the use of heavy metal reagents.
Tetrazine-mediated bioorthogonal prodrug-prodrug activation
Neumann, Kevin,Gambardella, Alessia,Lilienkampf, Annamaria,Bradley, Mark
, p. 7198 - 7203 (2018/10/02)
The selective and biocompatible activation of prodrugs within complex biological systems remains a key challenge in medical chemistry and chemical biology. Herein we report, for the first time, a dual prodrug activation strategy that fully satisfies the principle of bioorthogonality by the symbiotic formation of two active drugs. This dual and traceless prodrug activation strategy takes advantage of the INVDA chemistry of tetrazines (here a prodrug), generating a pyridazine-based miR21 inhibitor and the anti-cancer drug camptothecin and offers a new concept in prodrug activation.
An improved synthesis of (20S)-camptothecin and its analogue via an asymmetric α-hydroxylation with a chiral organocatalyst
Wang, Xinlong,Xu, Lingjun,Xiong, Fangjun,Wu, Yan,Chen, Fener
, p. 843 - 848 (2017/06/13)
An efficient and stereocontrolled synthesis of (20S)-camptothecin and an analogue has been developed. The key feature of this synthesis is the organocatalyzed asymmetric α-hydroxylation of the lactone precursor 4 to construct its stereocenter, providing tricyclic hydroxylactone 2 in 90% yield and with 88% enantioselectivity. The precursor 4 was efficiently synthesized from the known pyridine 5 in three steps.
Synthesis of indolizinoquinolinones through three- and four-component domino Knoevenagel / hetero-Diels–Alder reactions: novel access to (+)-camptothecin
Tietze, Lutz F.,Bischoff, Matthias,Khan, Taukeer A.,Liu, Deshan
, p. 434 - 445 (2017/07/07)
[Figure not available: see fulltext.] The fused heterocyclic indolizinoquinolinone system is a key structural feature of several highly bioactive alkaloids, including camptothecin. Camptothecin has been efficiently obtained by a three- or four-component domino Knoevenagel / hetero-Diels–Alder reaction of aldehyde, Meldrum's acid, and enol ether in the presence or absence of alcohol, followed by reductive cleavage of the amine protecting group. The obtained products were further transformed along several different routes leading to camptothecin.
